Isopropanol → HCID 11619381, compound

HRID 216120Notes

Reaction equation

HRID 216120 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][NH:13][C:14]2[CH:19]=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=3)[N:17]=[C:16](S(C)(=O)=O)[N:15]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[CH:34]([OH:37])([CH3:36])[CH3:35].[H-].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][NH:13][C:14]2[CH:19]=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=3)[N:17]=[C:16]([O:37][CH:34]([CH3:36])[CH3:35])[N:15]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 24758Sodium hydrideHCID 57636046HCID 57636046, compound2×

Product 1

HCID 11619381HCID 11619381, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of [2-(3,4-dimethoxy-phenyl)-ethyl]-[6-(3,4-dimethoxy-phenyl)-2-methanesulfonyl-pyrimidin-4-yl]-anine [200 mg, 0.42 mmol, Intermediate (33)], and isopropyl alcohol (1 mL) in N,N′-dimethylformamide (2 mL) at 0° C. is treated with sodium hydride (60%, 102 mg, 12.7 mmol). After 1 hour at 20° C., the mixture is concentrated, and extracted twice with EtOAc (50 mL). The combined extracts are washed twice with water, dried over magnesium sulfate, filtered, and concentrated. The residue is subjected to chromatography on silica gel eluting with 60% EtOAc in heptane to afford [2-(3,4-dimethoxy-phenyl)-ethyl]-[6-(3,4-dimethoxy-phenyl)-2-isopropoxy-pyrimidin-4-yl]-amine [0.15 g, 79%, Example 17(a)] LCMS: RT=2.57 minutes, MS: 454 (M+H). 1H NMR (300 MHz, CDCl3) □7.64 (1H, d, J=2.1 Hz), 7.55 (1H, dd, J=8.4, 2.4 Hz), 6.91 (1H, d, J=8.4 Hz), 6.86-6.76 (3H, m), 6.3 (1H, s), 5.43-5.34 (1H, m), 4.83 (1H, brs), 3.99 (3H, s), 3.95 (3H, s), 3.89 (3H, s), 3.75-3.65 (2H, m), 2.91 (2H, t, J=6.9 Hz) 1.45 (6H, d, J=6 Hz). IC50=6728 nM

Workup

  1. concentrationthe mixture is concentrated
  2. extractionextracted twice with EtOAc (50 mL)
  3. washThe combined extracts are washed twice with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f6c4ba957382456e94f471f3b90e58f7
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

Loading…